FACTORS INFLUENCING SURVIVAL OF VASCULAR BONE GRAFTS

这项建议旨在： 1.评估延长带血管同种异体骨移植(VBA)的存活时间 通过对宿主相对无毒的方法，材料性能 原位放置的VBA及其超微结构变化 嫁接。在确定了经典的、具体的和 免疫抑制的非特异性手段、单抗和 移植物照射延长移植物存活时间的研究进展 将探索异位模型。移植物将被放置在 原位体位和经典免疫抑制的持续时间 治疗方案将会确定。的材料特性 将对这些正位放置的移植物进行评估，并 将研究移植物的超微结构变化，以便 辨别这些复合材料中的拒绝过程的焦点 嫁接。 我们计划使用同种异体带血管的骨移植 模型研究(1)性别和荷尔蒙环境对健康的影响 纵向骨骼生长及(2)分子机制 与废用性骨质疏松症有关，这通常见于 移植的四肢。将从雌性大鼠身上移植四肢 对青春期前和青春期后的雄性大鼠和雌性大鼠进行对照 试图剖析软骨细胞的基因分型和影响因素 激素环境对骨骼生长的影响。去垂体大鼠 在手术后的进展周将被用作捐赠者 评估增长潜力的持续时间和可能的机制 参与生长板的衰老。检查废旧物品 骨质疏松时，将用免疫组织化学染色 确定适当合并了哪些矩阵组件 转化为骨；对于那些不存在的成分，原位 将使用杂交来确定这种控制是否处于 转录或翻译水平。 3.探索之前概念的重建潜力 称为“模塑血管化成骨”，其中 血管蒂与非血管化骨融合术 在预定大小和形状的模具中进行移植将导致 可行的带血管的骨移植。实验的目的是为了 确定这些移植物可以作为孤岛移植物还是自由移植物 移植物，移植物转移的最佳时机，愈合 以及这些移植物的材料特性，以及非 宿主骨物质将成为模塑的血管化移植物。

This proposal seeks to: 1. Evaluate prolonging vascularized bone allograft (VBA) survival by methods relatively nontoxic to the host, the material properties of orthotopically placed VBAs, and ultrastructural changes of these grafts. Having determined the roles of classic specific and nonspecific means of immunosuppression, monoclonal antibodies and the use of graft irradiation to prolong graft survival in a heterotopic model will be explored. Grafts will be placed in the orthotopic position, and the duration of classic immunosuppressive therapy regimens will be determined. The material properties of these orthotopically placed grafts will be evaluated, and ultrastructural changes in the graft will be studied in order to discern the focus of the rejection process in these composite grafts. 2 We plan to use a syngeneic vascularized bone transplantation model to study (1) the influences of gender and hormonal milieu on longitudinal skeletal growth and (2) the molecular mechanisms involved in disuse osteoporosis which is typically seen in the transplanted limbs. Limbs will be transplanted form female rats to pre- and post-pubertal male rats and to control females in an attempt to dissect the influences of chondrocyte genotype and hormonal environment on skeletal growth. Hypophysectomized rats at progressive weeks after surgery will be used as donors to evaluate the duration of growth potential and possible mechanisms involved in senescence at the growth plate. To examine disuse osteoporosis, immunohistochemical staining will be used to determine which matrix components are appropriately incorporated into bone; for those components which are not present, in situ hybridization will be used to establish whether this control is at the transcriptional or translational level. 3. Explore the reconstructive potential of the concept previously termed "molded vascularized osteoneogenesis" in which the incorporation of a vascular pedicle with nonvascularized bone grafts in a mold of predetermined size and shape will result in a viable vascularized bone graft. Experiments have been designed to determine if these grafts can be transferred as island or free grafts, the optimum timing for transfer of such grafts, the healing and material properties of these grafts, and the ability of non- host bone substances to become molded vascularized grafts.